This proposal is directed towards understanding further the biochemical basis of loss of metabolic function at low temperature using cold-sensitive mutants of Salmonella typhimurium as an experimental tool. We will also study certain unanswered questions regarding nucleotide metabolism. These include: the pathway and mechanism of turnover of messenger RNA; the role of polynucleotide phosphorylase in nucleotide metabolism; and the pathway of biosynthesis of dTTP. The approach we will employ is that of biochemical genetics employing a set of mutants that we have already isolated in the various pathways of nucleotide metabolism. The results have bearing on antifungal chemotherapy and hereditary metabolic diseases of man.